is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of ...action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from
, on the lifespan of
(
). We found that TG extended the lifespan of
and reduced lipofuscin accumulation. Moreover, TG increased the survival of
in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of
,
,
,
and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of
and
mutants, highlighting their role in the antiaging effects of TG in
. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg
, Rg
and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of
to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in
.
In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of ...cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2′-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy.
Colorectal cancer (CRC) is one of the most prevalent and deadliest illnesses all around the world. Growing proofs demonstrate that tumor-associated macrophages (TAMs) are of critical importance in ...CRC pathogenesis, but their mechanisms remain yet unknown. The current research was designed to recognize underlying biomarkers associated with TAMs in CRC. We screened macrophage-related gene modules through WGCNA, selected hub genes utilizing the LASSO algorithm and COX regression, and established a model. External validation was performed by expression analysis using datasets GSE14333, GSE74602, and GSE87211. After validating the bioinformatics results using real-time quantitative reverse transcription PCR, we identified SPP1, C5AR1, MMP3, TIMP1, ADAM8 as potential biomarkers associated with macrophages in CRC.
Endothelial progenitor cells (EPCs) have been associated with human sepsis but their role is incompletely understood. Stromal cell-derived factor (SDF)-1α facilitates EPC recruitment and is elevated ...in murine sepsis models. Previous studies have demonstrated that the SDF-1α analog CTCE-0214 (CTCE) is beneficial in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice.
We hypothesized that exogenously administered EPCs are also beneficial in CLP sepsis and that CTCE provides synergistic benefit.
Mice were subjected to CLP and administered EPCs at varying doses, CTCE, or a combination of the two. Mouse survival, plasma miRNA expression, IL-10 production, and lung vascular leakage were determined. The in vitro effect of CTCE on miRNA expression and EPC function were determined.
Survival was improved with EPC therapy at a threshold of 10(6) cells. In coculture studies, EPCs augmented LPS-induced macrophage IL-10 production. In vivo EPC administration in sepsis increased plasma IL-10, suppressed lung vascular leakage, attenuated liver and kidney injury, and augmented miR-126 and -125b expression, which regulate endothelial cell function and/or inflammation. When subthreshold numbers of EPCs were coadministered with CTCE in CLP mice they synergistically improved survival. We demonstrated that CTCE recruits endogenous EPCs in septic mice. In in vitro analysis, CTCE enhanced EPC proliferation, angiogenesis, and prosurvival signaling while inhibiting EPC senescence. These cellular effects were, in part, explained by the effect of CTCE on miR-126, -125b, -34a, and -155 expression in EPCs.
EPCs and CTCE represent important potential therapeutic strategies in sepsis.
The evidence shows that there is an associated relationship between hepatosteatosis and insulin resistance. While some existing genetic induction animal and patient models challenge this ...relationship, indicating that hepatosteatosis is dissociated from insulin resistance. However, the molecular mechanisms of this dissociation remain poorly understood due to a lack of available, reliable, and simplistic setup models. Currently, we used primary rat hepatocytes (rHPCs), co-cultured with rat hepatic stellate cells (HSC-T6) or human foreskin fibroblast cells (HFF-1) in stimulation with high insulin and glucose, to develop a model of steatosis charactered as dissociated lipid accumulation from insulin resistance. Oil-Red staining significantly showed intracellular lipid accumulated in the developed model. Gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and elongase of very-long-chain fatty acids 6 (ELOVL6), key genes responsible for lipogenesis, were detected and obviously increased in this model. Inversely, the insulin resistance related genes expression included phosphoenolpyruvate carboxykinase 1 (PCK1), pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), and glucose-6-phosphatase (G6pase) were decreased, suggesting a dissociation relationship between steatosis and insulin resistance in the developed model. As well, the drug metabolism of this developed model was investigated and showed up-regulation of cytochrome P450 3A (CYP3A) and down-regulation of cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2). Taken together, those results demonstrate that the in vitro model of dissociated steatosis from insulin resistance was successfully created by our co-cultured cells in high insulin and glucose medium, which will be a potential model for investigating the mechanism of insulin resistance dissociated steatosis, and discovering a novel drug for its treatment.
A dendrimer (termed G2) containing pyrene as the core and 9-phenylcarbazole (PCZ) on the periphery is shown to be a multi-functional fluorescent probe for iodide, iron(III) and mercury(II). It serves ...as the fluorometric/colorimetric dual-channel probe for these ions. As a fluorometric probe, the fluorescence of G2 is quenched both by iodide and iron(III). After that, the fluorescence of G2 which has been added iodide will recover when added mercury(II); as a colorimetric probe, the color of G2 solution can turn to yellow only by iodide which will change from yellow to colorless again when adding mercury(II). The color change is sensitive and observed visually at 0.1 mM for iodide. G2 also is an electroactive precursor for preparation of fluorescent films via electropolymerization. The resulting films can be used as the fluorescent films to sense the ions. This is attributed to the presence of a large specific surface, highly cross-linked microstructures and enhanced π conjugation. The electropolymerized film has blue fluorescence with excitation/emission maxima at 365/460 nm. The limits of detection (LOD) of G2 for iodide, iron(III) and mercury(II) were calculated to be 9.3, 37.1 and 22.0 nM in solution and 5.1, 12.0 and 6.1 nM in films, respectively. The linear range is from 2 to 10 μM for G2 electropolymerized films. The detection range is from 2 to 400 μM for iron(III) and mercury(II). The detection range is from 2 to 130 μM for iodide. For a third application, G2 displays compelling sensing performance in environmental systems and in living roundworms.
Graphical abstract
As schematic presentation, after adding iodide, the fluorescence of G2 is quenched and the color changes to yellow. When adding Hg
2+
to G2-iodide, the fluorescence and color of G2 recover. Iron(III) can also quench G2, but the color does not change.
This study aims to evaluate the effect of bilateral nasal packing on sleep oxygen saturation and its influencing factors on the first night after general anesthesia.
A total of 36 adult patients who ...underwent bilateral nasal packing with a nonabsorbable expanding sponge after general anesthesia surgery were prospectively studied. All these patients underwent overnight oximetry tests before and the first night after surgery. The following oximetry variables were collected for analysis: the lowest oxygen saturation (LSAT), the average oxygen saturation (ASAT), the oxygen desaturation index of ≥4% (ODI4), and the percentage of time with oxygen saturation below 90% (CT90).
Among the 36 patients, the incidences of both sleep hypoxemia and moderate-to-severe sleep hypoxemia increased with bilateral nasal packing after general anesthesia surgery. All the pulse oximetry variables we studied deteriorated significantly after surgery: both LSAT and ASAT decreased significantly (
< 0.05), while both ODI4 and CT90 increased significantly (
< 0.05). In a multiple logistic regression analysis, body mass index (BMI), LSAT, and modified Mallampati grade were found to be independently predictive for a larger decrease in LSAT (≥5%) after surgery (all
's < 0.05).
Bilateral nasal packing after general anesthesia could induce or aggravate sleep hypoxemia, especially in patients with obesity, relatively normal sleep oxygen saturation, and high modified Mallampati grades.
TiB
2
nanoparticles reinforced AS41A alloys were fabricated by ultrasonic assisted stir casting. The influence of ultrasonic treatment and TiB
2
nanoparticles on the microstructure and mechanical ...properties of AS41A magnesium alloy was investigated. The results showed that the ultrasonic treatment obviously refined microstructure, thereby improving the mechanical properties of the magnesium alloys. The addition of TiB
2
further increased the tensile strength slightly while maintaining the improved elongation as the ultrasound-treated matrix alloys.The ultimate tensile strength, yield strength and elongation of the obtained nanocomposites were improved by 27.4%, 43.5% and 84.6% compared with those of the as-cast matrix alloys, respectively.
Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, which is characterized by the accumulation of amyloid β (Aβ) plaques, oxidative stress, and neuronal loss. ...Therefore, clearing Aβ aggregates and reducing oxidative stress could be an effective therapeutic strategy for AD. Deuterohemin-AlaHisThrValGluLys (DhHP-6), a novel deuterohemin-containing peptide mimetic of the natural microperoxidase-11 (MP-11), shows higher antioxidant activity and stability compared to the natural microperoxidases. DhHP-6 possesses the ability of extending lifespan and alleviating paralysis in the Aβ1-42 transgenic
CL4176 model of AD, as shown in our previous study. Therefore, this study was aimed at exploring the neuroprotective effect of DhHP-6 in the APPswe/PSEN1dE9 transgenic mouse model of AD. DhHP-6 reduced the diameter and fiber structure of Aβ1-42 aggregation in vitro, as shown by dynamic light scattering and transmission electron microscope. DhHP-6 exerted its neuroprotective effect by inhibiting Aβ aggregation and plaque formation, and by reducing Aβ1-42 oligomers-induced neurotoxicity on HT22 (mouse hippocampal neuronal) and SH-SY5Y (human neuroblastoma) cells. In the AD mouse model, DhHP-6 significantly ameliorated cognitive decline and improved spatial learning ability in behavioral tests including the Morris water maze, Y-maze, novel object recognition, open field, and nest-building test. Moreover, DhHP-6 reduced the deposition of Aβ plaques in the cerebral cortex and hippocampus. More importantly, DhHP-6 restored the morphology of astrocytes and microglia, and significantly reduced the levels of pro-inflammatory cytokines. Our findings provide a basis for considering the non-toxic, peroxidase mimetic DhHP-6 as a new candidate drug against AD.
The dispersion behavior of SiC particles in molten Mg alloys during stirring casting using four-bladed stirrer was investigated by numerical simulation. The effects of stirring speeds (300, 500, 800 ...rpm) and stirring temperatures (590, 620, 640 °C) on the dispersion uniformity of the SiC particles were investigated. Simulation results show that the particle concentration fluctuates along both the height and radial directions of the stirred vessel to varying degrees. When the stirring casting was performed at 590 °C and at 300 rpm, a relatively uniform spatial distribution of SiC particles without large aggregations was obtained.
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